Objectives: We investigated the effect of a microcatheter-based selectively induced intra-arterial hypothermia on hemodynamic changes following transient cerebral ischemia in rats. Methods: Stroke was induced in male Sprague-Dawley rats by a two-hour middle cerebral artery occlusion (MCAO) using a microcatheter. After the two-hour MCAO, 0.9% cold saline (0 degrees C) was selectively infused through a microcatheter. Cerebral blood flow (CBF) in the ischemic brain region was continuously monitored by Laser-Doppler flowmetry (LDF) during the procedure. Following ischemia/reperfusion, serial functional neurologic testing was performed, and cerebral infarct volume was evaluated after 48 hours. Results: The local cold saline infusion, via a microcatheter, achieved a rapid induction of brain hypothermia (cerebral cortex from 37.1 +/- 0.3 to 30.7 +/- 0.4 degrees C; striatum from 37.5 +/- 0.3 to 30.9 +/- 0.5 degrees C). When compared to the non-treatment group, the local cold saline infusion treatment reduced both post-ischemic hyperperfusion (about 40%, P < 0.01) and delayed post-ischemic hypoperfusion (P < 0.01), improved functional neurological testing (P < 0.01), and reduced both cerebral infarction volume (40.6 +/- 5.3 vs. 61.7 +/- 8.6%, P < 0.01) and cerebral edema (7.8 +/- 2.6 vs. 15.4 +/- 3.2%, P < 0.01). Conclusion: Cold saline, when infused directly into the ischemic brain region, can confer robust neuroprotection by reducing immediate post-ischemic hyperperfusion and delayed post-ischemic hypoperfusion.